Whether one accepts a genetic or epigenetic basis for oncogenic transformation, both situations ultimately are expressed by the nucleotidyl transfer enzymes. A number of studies indicate an indirect and possibly direct involvement of this class of enzymes in the neoplastic process, clearly pointing to the need for the development of selective inhibitors to be examined as antitumor agents. The objective of the proposed work involves the rational design, synthesis and biological evaluation of such inhibitors. Zn ion 2 and Mg ion 2 are intimately involved in the binding of nucleoside triphosphates and substrates, and in the catalytic activity of these enzymes. A series of nucleosides in which the 5'-position contains metal coordinating groups are proposed which would likely tie up the enzyme bound metals leading to inhibition. Evidence is presented which suggests the possibility of selective inhibition within this class of enzymes. Twenty four 5'-nucleoside chelators will be synthesized. Proposed 5'-nucleoside chelators will be prepared using well established synthetic procedures. Compounds will be isolated and characterized by the usual means. All compounds will be examined for their ability to inhibit eight different nucleotidyl transferases. Active compounds will be further examined for specific inhibitory characteristics with this class of enzymes.